Browse > Article
http://dx.doi.org/10.5667/tang.2014.0008

Drug-herb interactions: Mechanisms involved and clinical implications of five commonly and traditionally used herbs  

Ong, Chin Eng (School of Pharmacy, Monash University Malaysia)
Pan, Yan (School of Biomedical Sciences, The University of Nottingham Malaysia Campus)
Publication Information
CELLMED / v.4, no.3, 2014 , pp. 17.1-17.8 More about this Journal
Abstract
Herbal remedies are commonly used by patients worldwide. Because these herbal preparations share the same metabolic and transport proteins with prescribed medicines, the potential for a drug-herb interaction is substantial and is an issue of significant concern. This review paper summarizes drug-herb interactions involving inhibition or induction of cytochrome P450 enzymes, drug transporters as well as modulation of drug pharmacodynamics. An increasing number of in vitro and animal studies, case reports and clinical trials evaluating such interactions have been reported, and implications of these studies are discussed in this review. The most commonly implicated drugs in the interaction include anticoagulants, antiplatelets, immunosuppressants, anti-neoplastics, protease inhibitors, and some antidepressants. Pharmacokinetic and/or pharmacodynamic interactions of five commonly used herbal remedies (danshen, garlic, Ginkgo biloba, ginseng, and St John's wort) with these drugs are presented, with focus of discussion being the potentials for interaction, their mechanisms and clinical implications. There is a necessity for adequate pharmacovigilance to be carried out in minimizing unanticipated but often preventable drug-herb interactions.
Keywords
cytochrome P450; drug-herb interaction; P-glycoprotein; pharmacodynamics; pharmacokinetics;
Citations & Related Records
연도 인용수 순위
  • Reference
1 Solomon D, Ford E, Adams J, Graves N. Potential of St John's wort for the treatment of depression: the economic perspective. Aust N Z J Psychiatry. 2011;45:123-130.   DOI   ScienceOn
2 Vaes LP, Chyka PA. Interactions of warfarin with garlic, ginger, ginkgo, or ginseng: nature of the evidence. Ann Pharmacother. 2000;34:1478-1482.   DOI
3 Ueng YF, Kuo YH, Wang SY, Lin YL, Chen CF. Induction of CYP1A by a diterpene quinine tanshinone IIA isolated from a medicinal herb Salvia miltiorrhiza in C57BL/6J but not in DBA/2J mice. Life Sci. 2004;74:885-896.   DOI   ScienceOn
4 van Beek TA, Montoro P. Chemical analysis and quality control of Ginkgo biloba leaves, extracts, and phytopharmaceuticals. J Chromatogr A. 2009;1216:2002-2032.   DOI   ScienceOn
5 Vlachojannis J, Cameron M, Chrubasik S. Drug interactions with St John's wort products. Pharmacol Res. 2011;63:254-256.   DOI   ScienceOn
6 Weinmann S, Roll S, Schwarzbach C, Vauth C, Willich SN. Effects of Ginkgo biloba in dementia: systematic review and meta-analysis. BMC Geriatr. 2010;10:14.   DOI   ScienceOn
7 Yin OQ, Tomlinson B, Waye MM, Chow AH, Chow MS. Pharmacogenetics and herb-drug interactions: experience with Ginkgo biloba and omeprazole. Pharmacogenetics. 2004;14:841-850.   DOI   ScienceOn
8 Zhou S, Koh HL, Gao Y, Gong ZY, Lee EJ. Herbal bioactivation: the good, the bad and the ugly. Life Sci. 2004;74:935-968.   DOI   ScienceOn
9 Yoshioka M, Ohnishi N, Koishi T, Obata Y, Nakagawa M, Matsumoto T, Tagagi K, Takara K, Ohkuni T, Yokoyama T, Kuroda K. Studies on interactions between functional foods or dietary supplements and medicines: IV. Effects of Ginkgo biloba leaf extract on the pharmacokinetics and pharmacodynamics of nifedipine in healthy volunteers. Biol Pharm Bull. 2004;27:2006-2009.   DOI   ScienceOn
10 Yu CM, Chan JC, Sanderson JE. Chinese herbs and warfarin potentiation by 'danshen'. J Intern Med. 1997;241:337-339.   DOI   ScienceOn
11 Yu CT, Chen J, Teng XW, Tong V, Chang TK. Lack of evidence for induction of CYP2B1, CYP3A23, and CYP1A2 gene expression by Panax ginseng and Panax quinquefolius extracts in adult rats and primary cultures of rat hepatocytes. Drug Metab Dispos. 2005;33:19-22.
12 Bauer S, Stormer E, Johne A, Kruger H, Budde K, Neumayer HH, Roots I, Mai I. Alterations in cyclosporinA pharmacokinetics and metabolism during treatment with St John's wort in renal transplant patients. Br J Clin Pharmacol. 2003;55:203-211.   DOI   ScienceOn
13 Becker BN, Greene J, Evanson J, Chidsey G, Stone WJ. Ginseng-induced diuretic resistance. JAMA. 1996;276:606-607.
14 Aruna D, Maidu MU. Pharmacodynamic interaction studies of Ginkgo biloba with cilostazol and clopidogrel in healthy human subjects. Br J Clin Pharmacol. 2006;63:333-338.
15 Attele AS, Wu JA, Yuan CS. Ginseng pharmacology: multiple constituents and multiple actions. Biochem Pharmacol. 1999;58:1685-1693.   DOI   ScienceOn
16 Beckert BW, Concannon MJ, Henry SL, Smith DS, Puckett CL. The effect of herbal medicines on platelet function: an in vivo experiment and review of the literature. Plast Reconstr Surg. 2007;120:2044-2050.   DOI   ScienceOn
17 Chan K, Lo AC, Yeung JH, Woo KS. The effects of Danshen (Salvia miltiorrhiza) on warfarin pharmacodynamics and pharmacokinetics of warfarin enantiomers in rats. J Pharm Pharmacol. 1995;47:402-406.   DOI
18 Black DJ, Kunze KL, Wienkers LC, Gidal BE, Seaton TL, McDonnell ND, Evans JS, Bauwens JE, TragerWF. Warfarinfluconazole. II. A metabolically based drug interaction: in vivo studies. Drug Metab Dispos.1996;24:422-428.
19 Block E. The chemistry of garlic and onions. Sci Am. 1985;252:114-119.
20 Bone KM. Potential interaction of Ginkgo biloba leaf with antiplatelet or anticoagulant drugs: what is the evidence? Mol Nutr Food Res. 2008;52:764-771.   DOI   ScienceOn
21 Borrelli F, Capasso R, Izzo AA. Garlic (Allium sativum L.): adverse effects and drug interactions in humans. Mol Nutr Food Res. 2007;51:1386-1397.   DOI   ScienceOn
22 Boruban MC, Yasar U, Babaoglu MO, Sencan O, Bozkurt A. Tamoxifen inhibits cytochrome P450 2C9 activity in breastcancer patients. J Chemother. 2006;18:421-424.   DOI   ScienceOn
23 Butterweck V, Schmidt M. St John's wort: role of active compounds for its mechanism of action and efficacy. Wien Med Wochenschr. 2007;157:356-361.   DOI   ScienceOn
24 Chang TK, Chen J, Benetton SA. In vitro effect of standardized ginseng extracts and individual ginsenosides on the catalytic activity of human CYP1A1, CYP1A2, and CYP1B1. Drug Metab Dispos. 2002;30:378-384.   DOI   ScienceOn
25 Cheng TO. Cardiovascular effects of Danshen. Int J Cardiol. 2007;121:9-22.   DOI   ScienceOn
26 deMaat MM, Hoetelmans RM, Math t RA, van Gorp EC, Meenhorst PL, Mulder JW, Beijnen JH. Drug interaction between St John's wort and nevirapine. AIDS. 2001;15:420-421.   DOI   ScienceOn
27 Cox MC, Low J, Lee J, Walshe J, Denduluri N, Berman A, Permenter MG, Petros WP, Price DK, Figg WD, Sparreboom A, Swain SM. Influence of garlic (Allium sativum) on the pharmacokinetics of docetaxel. Clin Cancer Res. 2006;12:4636-4640.   DOI   ScienceOn
28 Dannawi M. Possible serotonin syndrome after combination of buspirone and St John's wort. J Psychopharmacol. 2002;16:401.
29 DeFeudis FV, Drieu K. Ginkgo biloba extract (EGb 761) and CNS functions: basic studies and clinical applications. Curr Drug Targets. 2000;1:25-58.   DOI
30 Gallicano K, Foster B, Choudhri S. Effect of short-term administration of garlic supplements on single-dose ritonavir pharmacokinetics in healthy volunteers. Br J Clin Pharmacol. 2003;55:199-202.   DOI   ScienceOn
31 Deng JF. Clinical and laboratory investigations in herbal poisonings. Toxicology. 2002;181-182:571-576.   DOI   ScienceOn
32 Dresser GK, Spence JD, Bailey DG. Pharmacokineticpharmacodynamic consequences and clinical relevance of cytochrome P450 3A4 inhibition. Clin Pharmacokinet. 2000;38:41-57.   DOI   ScienceOn
33 Foster BC, Vandenhoek S, Tang R, Budzinski JW, Krantis A, Li KY. Effect of several Chinese natural health products of human cytochrome P450 metabolism. J Pharm Pharm Sci. 2002;5:185-189.
34 Gao S, Liu Z, Li H, Little PJ, Liu P, Xu S. Cardiovascular actions and therapeutic potential of tanshinone IIA. Atherosclerosis. 2012;220:3-10.   DOI   ScienceOn
35 Hafner V, Jager M, Matthee AK, Ding R, Burhenne J, Haefeli WE, Mikus G. Effect of simultaneous induction andinhibition of CYP3A by St John's wort and ritonavir on CYP3A activity. Clin Pharmacol Ther. 2010;87:191-196.   DOI   ScienceOn
36 Greenblatt DJ, von Moltke LL, Luo Y, Perloff ES, Horan KA, Bruce A, Reynolds RC, Harmatz JS, Avula B, Khan IA, Goldman P. Ginkgo biloba does not alter clearance of flurbiprofen, a cytochrome P450-2C9 substrate. J Clin Pharmacol. 2006;46:214-221.   DOI
37 Gurley BJ, Gardner SF, Hubbard MA, Williams DK, Gentry WB, Cui Y, Ang CY. Cytochrome P450 phenotypic ratios for predicting herb-drug interactions in humans. Clin Pharmacol Ther. 2002;72:276-287.   DOI   ScienceOn
38 Gurley BJ, Gardner SF, Hubbard MA, Williams DK, Gentry WB, Cui Y, Ang CY. Clinical assessment of effects of botanical supplementation on cytochrome P450 phenotypes in the elderly: St John's wort, garlic oil, Panax ginseng and Ginkgo biloba. Drugs Aging. 2005;22:525-539.   DOI   ScienceOn
39 Izzo AA, Borrelli F, Capasso R. Herbal medicine: the dangers of drug interaction. Trends Pharmacol Sci. 2002;23:358-391.   DOI   ScienceOn
40 He N, Xie HG, Collins X, Edeki T, Yan Z. Effects of individual ginsenosides, ginkgolides and flavonoids on CYP2C19 and CYP2D6 activity in human liver microsomes. Clin Exp Pharmacol Physiol. 2006;33:813-815.   DOI   ScienceOn
41 Izzat MB, Yim AP, El-Zufari MH. A taste of Chinese medicine!. Ann Thorac Surg. 1998;66:941-942.   DOI   ScienceOn
42 Janetzky K, Morreale AP. Probable interaction between warfarin and ginseng. Am J Heath Syst Pharm. 1997;54:692-693.
43 Kauffman DW, Kelly JP, Rosenberg L, Anderson TE, Mitchell AA. Recent patterns of medication use in the ambulatory adult population of the United States. JAMA. 2002;287:337-344.   DOI   ScienceOn
44 Kuo YH, Lin YL, Don MJ, Chen RM, Ueng YF. Induction of cytochrome P450-dependent monooxygenase by extracts of the medicinal herb Salvia miltiorrhiza. J Pharm Pharmacol. 2006;58:521-527.   DOI   ScienceOn
45 Klotz U. Pharmacokinetics and drug metabolism in the elderly. Drug Metab Rev. 2009;41:67-76.   DOI   ScienceOn
46 Kremers P. In vitro tests for predicting drug-drug interactions: the need for validated procedures. Pharmacol Toxicol. 2002;91:209-217.   DOI   ScienceOn
47 Kuo SC, Teng CM, Leed JC, Ko FN, Chen SC, Wu TS. Antiplatelet components in Panax ginseng. Planta Med. 1990;56:164-167.   DOI   ScienceOn
48 Lam FF, Yeung JH, Cheung JH, Or PM. Pharmacological evidence for calcium channel inhibition by Danshen (Salvia miltiorrhiza) on rat isolated femoral artery. J Cardiovasc Pharmacol. 2006;47:139-145.   DOI   ScienceOn
49 Mai I, Bauer S, Perloff ES, Johne A, Uehleke B, Frank B, Budde K, Roots I. Hyperforin content determines the magnitude of the St John's wort-cyclosporine drug interaction. Clin Pharmacol Ther. 2004;76:330-340.   DOI   ScienceOn
50 Lei HP, Ji W, Lin J, Chen H, Tan ZR, Hu DL, Liu LJ, Zhou HH. Effects of Ginkgo biloba extract on the pharmacokinetics of bupropion in healthy volunteers. Br J Clin Pharmacol. 2009;68:201-206.   DOI   ScienceOn
51 Linde K, Berner MM, Kriston L. St. John's wort for major depression. Cochrane Database Syst Rev. 2008;CD000448.
52 Lo AC, Chan K, Yeung JH, Woo KS. The effects of Danshen (Salvia miltiorrhiza) on pharmacokinetics and pharmacodynamics of warfarin in rats. Eur J Drug Metab Pharmacokinet. 1992;17:257-262.   DOI   ScienceOn
53 Morris J, Burke V, Mori TA, Vandongen R, Beilin LJ. Effects of garlic extract on platelet aggregation: a randomized placebo-controlled double-blind study. Clin Exp Pharmacol Physiol. 1995;22:414-417.   DOI   ScienceOn
54 Mai I, Stormer E, Bauer S, Kruger H, Budde K, Roots I. Impact of St John's wort treatment on the pharmacokinetics of tacrolimus and mycophenolic acid in renal transplant patients. Nephrol Dial Transplant. 2003;18:819-822.   DOI   ScienceOn
55 Markowitz JS, Donovan JL, Lindsay DeVane C, Sipkes L, Chavin KD. Multiple-dose administration of Ginkgo biloba did not affect cytochrome P-450 2D6 or 3A4 activity in normal volunteers. J Clin Psychopharmacol. 2003;23:576-581.   DOI   ScienceOn
56 Mathhews MK Jr. Association of ginkgo biloba with intracerebral haemorrhage. Neurology. 1998;50:1933-1934.   DOI   ScienceOn
57 Piscitelli SC, Burstein AH, Chaitt D, Alfaro RM, Falloon J. Indinavir concentrations and St John's wort. Lancet. 2000;355:547-548.   DOI   ScienceOn
58 Mullins ME, Horowitz BZ, Linden DH, Smith GW, Norton RL, Stump J. Life-threatening interaction of mibefradil and b-blockers with dihydropyridine calcium channel blockers. JAMA. 1998;280:157-158.   DOI   ScienceOn
59 Palmer ME, Haller C, McKinney PE, Klein-Schwartz W, Tschirgi A, Smolinske SC, Woolf A, Sprague BM, Ko R, Everson G, Nelson LS, Dodd-Butera T, Bartlett WD, Landzberg BR. Adverse events associated with dietary supplements: an observational study. Lancet. 2003;361:101-106.   DOI   ScienceOn
60 Pathak A, Leger P, Bagheri H, Senard JM, Boccalon H, Montastruc JL. Garlic interaction with fluindione: a case report. Therapie. 2003;58:380-381.   DOI
61 Robertson SM, Davey RT, Voell J, Formentini E, Alfaro RM, Penzak SR. Effect of Ginkgo biloba extract on lopinavir, midazolam and fexofenadine pharmacokinetics in healthy subjects. Curr Med Res Opin. 2008;24:591-599.   DOI   ScienceOn
62 Piscitelli SC, Burstein AH, Welden N, Gallicano KD, Falloon J. The effect of garlic supplements on the pharmacokinetics of saquinavir. Clin Infect Dis. 2002;34:234-238.   DOI   ScienceOn
63 Qi LW, Wang CZ, Yuan CS. Isolation and analysis of ginseng: advances and challenges. Nat Prod Rep. 2011;28:467-495.   DOI   ScienceOn
64 Qiu F, Wang G, Zhao Y, Sun H, Mao G, A J, Sun J. Effect of danshen extract on pharmacokinetics of theophylline in healthy volunteers. Br J Clin Pharmacol. 2008;65:270-274.   DOI   ScienceOn
65 Rosado MF. Thrombosis of a prosthetic aortic valve disclosing a hazardous interaction between warfarin and a commercial ginseng product. Cardiology. 2003;99:111.   DOI   ScienceOn
66 Rossenblatt M, Mindel J. Spontaneous hyphema associated with ingestion of Ginkgo biloba extract. N Engl J Med. 1997;336:1108.
67 Solecki RS, Shanidar IV.A Neanderthal flower burial in northern Iraq. Science. 1975;190:880-881.   DOI   ScienceOn
68 Shi S, Klotz U. Drug interactions with herbal medicines. Clin Pharmacokinet. 2012;51:77-104.   DOI   ScienceOn
69 Singh YP, Singh RA. In silico studies of organosulfurfunctional active compounds in garlic. Biofactors. 2010;36:297-311.   DOI
70 Smith M, Lin KM, Zheng YP. An open trial of nifedipine-herb interactions: nifedipine with St John's wort, ginseng or ginkgo biloba. Clin Pharmacol Ther. 2001;69:P89.   DOI   ScienceOn
71 Bonetto N, Santelli L, Battistin L, Cagnin A. Serotonin syndrome and rhabdomyolysis induced by concomitant use of triptans, fluoxetine and Hypericum. Cephalalgia. 2007;27:1421-1423.   DOI   ScienceOn
72 Hebert MF, Park JM, Chen YL, Akhtar S, Larson AM. Effects of St. John's wort (Hypericum perforatum) on tacrolimus pharmacokinetics in healthy volunteers. J Clin Pharmacol. 2004;44:89-94.   DOI   ScienceOn
73 Mohutsky MA, Anderson GD, Miller JW, Elmer GW. Ginkgo biloba: evaluation of CYP2C9 drug interactions in vitro and in vivo. Am J Ther. 2006;13:24-31.   DOI   ScienceOn